Tumor-associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in several animal model systems: one is a tumor virus induced leukemia of mice; another is human tumor xenographs in nude athymic mice. The various cytocidal agents being employed are radioisotopes. Their relative therapeutic efficacy when conjugated to antibodies is being assayed and compared to that of monoclonal antibodies alone. The isotopes now being used include the highly tumoricidal alpha emitting parent radioisotopes Pb-212 or Bi-212, as well as the beta particle emitter, Y-90. The syntheses of different chelates and radiochemical separations required for these objectives are being devised and reduced to clinical practice. Results from isotopic therapy are being compared with those obtained by use of antibody conjugated toxins or drugs with respect to tumor growth, regression, or cure. These studies will provide for human medicine a basis for design of rational therapy of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases. New chelates for use in this project have been synthesized and used, and have thus far proven useful for radiobiology studies of cell killing with alpha particle labeled antibody and for imaging of tumors in mice. Studies of tumor imaging in patients has begun. Pre-clinical examination of Y-90 labeled antibodies for therapy are in progress.